{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:05:38Z","timestamp":1789704338925,"version":"4.0.1"},"reference-count":45,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:00:00Z","timestamp":1747180800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K16549"],"award-info":[{"award-number":["21K16549"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Bone cement implantation syndrome is a critical complication of orthopaedic surgery, characterised by hypotension and hypoxemia. This syndrome is hypothesised to result from obstruction caused by fat droplets and the biochemical release of histamine caused by bone cement components. This study aimed to elucidate the histamine release mechanism, focusing on Mas\u2010related G protein\u2010coupled receptor X2 expressed on mast cells, which is hypothesised to be activated by bone cement components. Using a mast cell\u2010deficient mouse femur fracture model, we examined bone cement's effect on serum histamine. Rat basophil\u2010like cells expressing Mas\u2010related G protein\u2010coupled receptor X2 were exposed to monomethyl methacrylate, a bone cement component, to assess degranulation via <jats:italic>\u03b2<\/jats:italic>\u2010hexosaminidase release. Our findings demonstrated that histamine levels significantly increased in wild\u2010type mice post\u2010cement application, from 27.7\u2009\u00b1\u200911.1 to 35.3\u2009\u00b1\u200912.9\u2009ng\/mL (<jats:italic>p<\/jats:italic>\u2009=\u20090.016). Furthermore, Mas\u2010related G protein\u2010coupled receptor X2 expressing cells showed a marked increase in <jats:italic>\u03b2<\/jats:italic>\u2010hexosaminidase release upon monomethyl methacrylate stimulation (<jats:italic>p<\/jats:italic>\u2009=\u20094.30\u2009\u00d7\u200910<jats:sup>\u22125<\/jats:sup>). These results support the hypothesis that activating Mas\u2010related G protein\u2010coupled receptor X2 by monomethyl methacrylate contributes to bone cement implantation syndrome via histamine release. Bone cement implantation syndrome can manifest as a condition involving either peripheral vascular embolism, the release of chemical mediators, or a combination of both. Our research elucidates the role of chemical mediators, particularly histamine\u2010induced vasodilation, in the pathophysiology of bone cement implantation syndrome, providing valuable insights that pave the way for targeted interventions to mitigate this severe complication during orthopaedic surgery.<\/jats:p>","DOI":"10.1111\/1440-1681.70046","type":"journal-article","created":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T11:39:08Z","timestamp":1747222748000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>MRGPRX2<\/scp>\u2010Mediated Mast Cell Degranulation by Monomethyl Methacrylate: Unveiling a Pathway in Bone Cement Implantation Syndrome"],"prefix":"10.1111","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4871-9685","authenticated-orcid":false,"given":"Yasuyuki","family":"Suzuki","sequence":"first","affiliation":[{"name":"Department of Anaesthesiology Saiseikai Matsuyama Hospital  Matsuyama City Japan"},{"name":"Department of Pharmacology Ehime University Graduate School of Medicine  Toon City Japan"},{"name":"Research Division Saiseikai Research Institute of Health Care and Welfare  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Shuang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Ehime University Graduate School of Medicine  Toon City Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Takemasa","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Ehime University Graduate School of Medicine  Toon City Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Takasaki","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia and Perioperative Medicine Ehime University Graduate School of Medicine  Toon City Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Yorozuya","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia and Perioperative Medicine Ehime University Graduate School of Medicine  Toon City Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Mogi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Ehime University Graduate School of Medicine  Toon City Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,14]]},"reference":[{"issue":"6","key":"e_1_2_11_2_1","first-page":"2105","article-title":"Bone Cement and Its Anesthetic Complications: A Narrative Review","volume":"12","author":"Al\u2010Husinat L.","year":"2023","journal-title":"Journal of Clinical Medicine Research"},{"issue":"6","key":"e_1_2_11_3_1","first-page":"433","article-title":"Understanding Bone Cement Implantation Syndrome","volume":"86","author":"Hines C. 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